What is the evaluation and management of adults with Hepatitis B surface antigen (HBsAg) positivity?

Evaluation and Management of Adults with HBsAg Positivity

Adults with positive HBsAg for more than 6 months should undergo comprehensive evaluation including HBeAg/anti-HBe status, HBV DNA quantification, liver function tests, and fibrosis assessment to determine their disease phase and guide management decisions. 1

Initial Evaluation

Diagnostic Confirmation

• HBsAg positivity for longer than 6 months confirms chronic HBV infection 1
• Chronic infection should be differentiated from acute infection by testing for IgM anti-HBc (positive in acute infection) 1

Laboratory Assessment

• Complete blood count, liver enzymes (AST/ALT), alkaline phosphatase, gamma-glutamyl transpeptidase, bilirubin, albumin, creatinine, and prothrombin time 1
• Serologic markers: HBeAg/anti-HBe status and quantitative HBV DNA 1
• HBsAg quantification may provide additional prognostic information 2, 3
• Tests to rule out coinfections: anti-HCV, anti-HDV (in high-risk individuals), and anti-HIV 1
• Test for hepatitis A immunity (IgG anti-HAV) and vaccinate if negative 1

Liver Disease Assessment

• Non-invasive assessment of liver fibrosis using transient elastography or serum biomarkers 1
• Liver biopsy may be considered in selected cases with indeterminate disease status or suspected additional liver pathology 1
• Baseline ultrasound and serum α-fetoprotein for HCC screening in patients ≥20 years old 1

Disease Classification

HBeAg-Positive Chronic HBV Infection (Immune-Tolerant Phase)

• Characterized by: HBeAg positivity, very high HBV DNA levels (≥10,000 IU/mL), normal ALT, minimal liver inflammation 1
• Typically seen in perinatally acquired infection 1
• High risk of transmission due to high viral load 1

HBeAg-Positive Chronic Hepatitis B (Immune-Active Phase)

• Characterized by: HBeAg positivity, high HBV DNA (≥20,000 IU/mL), elevated ALT, moderate to severe liver inflammation 1
• Higher risk of fibrosis progression 1
• May progress to HBeAg seroconversion or to HBeAg-negative chronic hepatitis B 1

HBeAg-Negative Chronic HBV Infection (Inactive Carrier State)

• Characterized by: HBeAg negativity, anti-HBe positivity, low HBV DNA (<2,000 IU/mL), normal ALT 1
• Low risk of progression to cirrhosis or HCC if remaining in this phase 1
• HBsAg levels typically <1,000 IU/mL 1, 3
• Requires monitoring as reactivation can occur 1

HBeAg-Negative Chronic Hepatitis B

• Characterized by: HBeAg negativity, HBV DNA ≥2,000 IU/mL, elevated ALT, moderate to severe liver inflammation 1
• Associated with viral mutations in precore/basal core promoter regions 1
• Higher risk of progression to cirrhosis and HCC 1

Management Recommendations

Monitoring

• For patients not meeting treatment criteria: regular monitoring of ALT every 3-6 months and HBV DNA levels 1
• HCC surveillance with ultrasound ± AFP every 6 months for high-risk patients (cirrhosis, family history of HCC, age >40 years for men, >50 years for women) 1
• Periodic assessment of liver fibrosis using non-invasive methods 1

Antiviral Treatment

• Consider treatment for patients with:
  • HBeAg-positive chronic hepatitis B with elevated ALT and HBV DNA ≥20,000 IU/mL 1
  • HBeAg-negative chronic hepatitis B with elevated ALT and HBV DNA ≥2,000 IU/mL 1
  • Cirrhosis with any detectable HBV DNA 1
• First-line treatments include entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide 4
• Monitor for medication side effects, particularly renal function with tenofovir disoproxil fumarate 4

Prevention Measures

• Vaccinate household and sexual contacts against HBV 1
• Vaccinate against hepatitis A if not immune 1
• Counsel on alcohol abstinence or limited consumption 1
• Recommend smoking cessation 1

Special Considerations

HBsAg Quantification

• Lower HBsAg levels (<3.0 log10 IU/mL) in HBeAg-negative patients may indicate minimal liver damage 3
• Declining HBsAg levels may predict eventual HBsAg clearance 5, 6
• HBsAg levels correlate with intrahepatic cccDNA and disease activity 3, 6

Treatment Discontinuation

• Caution with treatment discontinuation due to risk of severe hepatitis flares 4
• Close monitoring of hepatic function with both clinical and laboratory follow-up for several months if treatment is discontinued 4

Occult HBV Infection

• Consider the possibility of occult HBV infection in patients with isolated anti-HBc positivity 1, 7
• HBV DNA testing may be helpful in these cases 1, 7

By following this systematic approach to evaluation and management, patients with chronic HBV infection can be appropriately classified, monitored, and treated to reduce the risk of progression to cirrhosis, liver failure, and hepatocellular carcinoma.